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Biomedical subjects

M Seemann

Publications and source records attributed to M Seemann.

16 recordsLinked to original sources

Hybrid rendering of the cervico-cranial arteries using spiral computed tomography.

PURPOSE: The purpose of this study was to develop a shaded-surface and volume display (hybrid rendering method) of the whole vascular system of the cervico-cranial arteries using spiral computed tomography (SCT). MATERIALS AND METHODS: We examined 12 patients with anatomic abnormalities and pathological conditions of the arterial vascular system. The cervico-cranial arteries were segmented using an interactive threshold interval density volume-growing method and visualized with a color-coded shaded-surface display (SSD) rendering method. The adjacent bone structures were visualized using a transparent volume rendering method. RESULTS: In all cases, the entire volume of the vascular system of the cervico-cranial arteries and the anatomic abnormalities and pathological conditions could be visualized. CONCLUSION: Hybrid rendering of the circulation of the cervico-cranial arteries using image data sets from a subsecond spiral CT scanner is useful for the visualization of anatomical and pathological abnormalities and offer a promising minimally invasive alternative compared with other diagnostic procedures.

Adult

Molecular heterogeneity of neurotransporters: implications for neurodegeneration.

Neurotransporters are high-affinity transport proteins located in the plasma membrane of both presynaptic nerve and glial cells that mediate the removal of neurotransmitters from the synaptic cleft or represent intracellular transport systems that concentrate neurotransmitters in synaptic vesicles. They comprise three subgroups, Na+/Cl(-)- or Na+/K(+)-dependent cell surface transporters and H(+)-dependent transporters associated with synaptic vesicles. The new insights into neurotransporter diversity provide the means for novel approaches of studying neurotransmitter uptake processes at the molecular level, such as substrate translocation and antagonist binding as well as regulation of gene expression, of intracellular trafficking, and of posttranslational modification. Moreover, modeling neurotransporter-related disorders and therapeutic strategies in genetically engineered animals are now feasible research strategies. Through an improved understanding of the modulation of neurotransporter function in the brain, it may be possible to identify the molecular factors underlying the etiopathogenesis and pathophysiology of neurodegenerative disorders. Due to their specificity for distinct neuronal systems, neurotransporters and their genes are potential targets for novel therapeutic strategies.

Animals

[CT subtraction angiography (CTSA). Results with an automated "elastic" subtraction algorithm].

PURPOSE: To develop and implement a method to obtain digital subtraction (DS) spiral computed tomography angiograms (SCTA) in order to avoid superimposition of bony structures and vascular calcifications on SCTA maximum intensity projections (MIPs) and shaded surface display (SSD). METHOD: Two SCTA data sets, one before and one during the injection of a contrast agent bolus, were obtained with identical scan parameters. Since ordinary subtraction of the two data sets fails to reliably separate bones and calcifications from the vascular lumen because of motion, a so-called elastic subtraction procedure was designed to correct 3D misregistration between the two data sets. It automatically accommodates for local position changes between baseline and contrast images, including regionally inconsistent non-linear displacements and arbitrary rotations. This method was tested in seven patients and evaluated against ordinary DS in terms of image quality and artifacts. RESULTS: In all patients "elastic" CTSA proved superior to ordinary DS. It provides automated and reliable separation of vessels from bones and calcifications. This improves the delineation of vessels in the neck and the skull base and of intracranial vessels. DS-SCTA facilitates MIPs and SSD without artifacts introduced by thresholding. CONCLUSION: Elastic DS-SCTA is a robust method for automated unmasking of vessels from bones and warrants clinical trials and comparison with MR- and conventional angiography.

Algorithms

[MRI of fingers in systemic scleroderma. Initial results with contrast-enhanced studies using a dedicated MRI system].

PURPOSE: To estimate disease activity in patients with systemic sclerosis using contrast-enhanced MRI of the skin. MATERIAL AND METHODS: In a pre-study, sequences of a low-field (0.2 T) scanner (Artoscan, Esaote, Genova, Italy) were optimized for detection of intravenous contrast (0.1 mmol/l Gd-DTPA) in six patients with the autoimmune disease systemic scleroderma. Based on the results of the pre-study, 17 patients with scleroderma (7 sclerotic/10 active inflammatory disease) were scanned using gradient-spoiled 3D GRE sequences (FA 90 degrees, TR 100 ms, TE 18 ms), which had been established as most sensitive for intravenous contrast. Contrast enhancement of the skin was determined quantitatively by contrast-to-noise ratios (CNR), comparing post- to pre-contrast and dynamic scans (for 6 min, 1 acquisition/min). Patients in the chronic state with sclerodactylia and active inflammation of the hands were considered separately and compared to a control group (n = 10) matched according to age. RESULTS: CNR increase after intravenous contrast was significantly higher in patients with active disease (86 +/- 16% increase) than sclerosing disease (29 +/- 3%, p < 0.05) and the control group (4 +/- 2%, p < 0.05). The dynamic examination showed a significantly slower decrease after the peak rise in the first minute in patients with active disease (CNR 15.4 +/- 0.7 to 14.2 +/- 1.4) than in those with chronic disease (14.1 +/- 0.5 to 11.3 +/- 0.9, p < 0.05). DISCUSSION: Capillary leakage is the most likely explanation for the increased enhancement in patients with active scleroderma. Using sequences optimized for contrast detection, disease activity in the course of scleroderma and response to therapy can be determined by MRI in the future.

Adult

Gene structure and 5'-flanking regulatory region of the murine serotonin transporter.

By modulating the magnitude and duration of postsynaptic responses, carrier-facilitated serotonin (5-HT) transport into and release from the presynaptic neuron is central to the fine tuning of serotonergic neurotransmission. The 5-HT transporter (5-HTT) is the prime target for widely used antidepressants, psychostimulants, drugs of abuse and neurotoxins. We have isolated the gene encoding the murine 5-HTT and determined the sequence of all exons including adjacent intronic regions and approximately 3.6 kb of the 5'-flanking regulatory region. The murine 5-HTT gene is composed of 14 exons spanning approximately 34 kb. The single gene transcript after splicing is 2744 bp in length and it contains 186 bp of 5' untranslated region (5'-UTR) and 668 bp of 3'-UTR. A TATA-like motif and several potential binding sites for transcription factors including AP1, AP2, AP4, SP1 as well as CRE- and GRE-like motifs are present in the GC-rich 5'-flanking region. The characterization of murine 5-HTT cDNA and genomic organization will facilitate studies of 5-HT uptake function with molecular pharmacologic and transgenic strategies as well as investigations of its role in quantitative traits and psychiatric disorders.

Amino Acid Sequence

[Increased liver density in computed tomography as a result of anti-arrhythmia therapy with amiodarone].

PURPOSE: To assess whether the hepatic density on CT scans of patients receiving amiodarone therapy differs significantly from the hepatic density of a control group not receiving the drug. METHODS: Hepatic density was assessed by CT in 31 patients receiving amiodarone, 7 receiving short-term (12-14 days), 8 receiving mid-term (20-89 days) and 16 receiving long-term therapy (3-26 months), as well as in a control group of 15 patients. RESULTS: Mean liver density of all patients under amiodarone therapy (77.9 +/- 11.7 HU) was significantly higher (p < 0.005) than in the control group (56.6 +/- 2.8 HU). The smallest increase in density was found in patients with short-term therapy (64.8 +/- 3.4 HU; p < 0.05), the greatest increase in patients with long-term therapy (85.0 +/- 8.9 HU; p < 0.001). CONCLUSION: In patients receiving amiodarone therapy, a significantly increased hepatic density on CT scans is observed. This finding has to be considered as a differential diagnosis to other hepatopathies with increased density of the liver.

Adult

Biosynthesis of isoprenoids (carotenoids, sterols, prenyl side-chains of chlorophylls and plastoquinone) via a novel pyruvate/glyceraldehyde 3-phosphate non-mevalonate pathway in the green alga Scenedesmus obliquus.

Isoprenoid biosynthesis was investigated in the green alga Scenedesmus obliquus grown heterotrophically on 13C-labelled glucose and acetate. Several isoprenoid compounds were isolated and investigated by 13C-NMR spectroscopy. According to the 13C-labelling pattern indicated by the 13C-NMR spectra, the biosynthesis of all plastidic isoprenoids investigated (prenyl side-chains of chlorophylls and plastoquinone-9, and the carotenoids beta-carotene and lutein), as well as of the non-plastidic cytoplasmic sterols, does not proceed via the classical acetate/mevalonate pathway (which leads from acetyl-CoA via mevalonate to isopentenyl diphosphate), but via the novel glyceraldehyde 3-phosphate/pyruvate route recently detected in eubacteria. Formation of isopentenyl diphosphate involves the condensation of a C2 unit derived from pyruvate decarboxylation with glyceraldehyde 3-phosphate and a transposition yielding the branched C5 skeleton of isoprenic units.

Carbon Isotopes

Spirometrically controlled high resolution computed tomography - quantitative assessment of density distribution in patients with diffuse fibrosing alveolitis.

STUDY OBJECTIVE: Lung density assessed by high resolution computed tomography (HRCT) is sufficiently sensitive for the diagnosis of interstitial lung disease, but may be hampered by uneven disease distribution. We determined the mean and subpleural density values in patients with diffuse fibrosing alveolitis (FA) and evaluated the diagnostic accuracy of both parameters, expressed as post-test odds ratios. MATERIALS AND METHODS: Pulmonary HRCT was performed on 21 FA patients and compared to scans of 27 healthy volunteers. The HRCT procedure was standardized by taking 3 scans at the carina +/- 5 cm, and by defining inspiration levels at 50% vital capacity. Mean lung density (MLD) and subpleural lung density (SLD) were calculated for all participants. RESULTS: MLD and SLD values for healthy subjects were significantly higher compared with the patient group. Odds ratios were 7.8:1 and 3.9:1 for SLD and MLD, respectively, demonstrating a superior discrimination power of SLD in the diagnosis of FA. CONCLUSION: Diagnostic accuracy of quantitative HRCT measurements in FA was improved by the separate evaluation of subpleural lung density, which is a better indicator of the presence or absence of lung fibrosis than is mean lung density.

Adult

[A method of computer-assisted, 3-dimensional subtraction angiography using spiral roentgen computerized tomography].

The objective of this study was to develop a method for 3D subtraction CT angiography and to optimize the visualization after semi-automatic segmentation. Ten patients with aneurysms of the abdominal aorta were examined using spiral CT. To reconstruct the vessels, as well as adjacent organs such as the liver and kidneys, one image data volume was acquired before and after injection of the contrast agent. The CT scans were obtained with a Siemens Somatom Plus 4. To improve the results of automatic segmentation, as well as visualization by maximum intensity projection (i.e. removal of bony structures), subtraction of both image volumes is necessary. However, small translation shifts disturb the subtraction process and produce artificial contours. To calculate the disparities along the three coordinate axes of two corresponding image volumes, a cepstrum filter is applied to a pair of image volumes. After detection of the disparities, which manifest as bright spots, the real shift of the two subsignals can be calculated. Translation of the corresponding image volume pairs to their correct positions improves the subtraction process. In all cases the size of the aneurysm and the abdominal organs could be better segmented and visualized. Application of the cepstrum filter and subtraction of the image volumes before and after contrast medium injection completely removes the bony structures in the image data and results in superior visualization results.

Angiography, Digital Subtraction

Functional promoter and polyadenylation site mapping of the human serotonin (5-HT) transporter gene.

We have isolated and characterized the 5'-flanking region and the proximal polyadenylation site of the human 5-HT transporter gene. The major gene transcript is 2,793 bp in length and it contains 208 bp of 5'-untranslated region (5'-UTR) and 694 bases of 3'-UTR. While only a single mRNA species occurs in rats and mice, the most proximal signal for polyadenylation in the human gene appears to be highly degenerate in comparison to the rat and murine motif. This polyadenylation signal-like motif may lead to alternate usage of additional polyadenylation sites resulting in multiple mRNA species in humans. A TATA-like motif and several potential binding sites for transcription factors including AP1, AP2, SP1, and a cAMP response element (CRE)-like motif are present in the 5'-flanking region. A approximately 1.7 kb fragment beginning 217 bp downstream from the transcription start site, which had been ligated into a luciferase reporter vector and transiently expressed in JAR human placental choriocarcinoma cells, displayed both constitutive and forskolin/cholera toxin-induced promoter activity. Functional promoter mapping revealed that there are negative attenuating elements between bp -1,428 and -1,185 and positive elements between bp -1,184 and -78 from the transcription initiation site. Studies with deletional mutants also indicated that core promoter sequences are contained within 78 bp of the transcription start site and that regulation of cAMP-inducible promoter activity depends on multiple cis-acting elements including two AP1 binding sites and a single CRE-like element located at bp -99. Our findings suggest that (1) the 5-HT transporter gene promoter is active in human JAR cells, but inactive in 5-HT transporter-deficient human SK-N-SH neuroblastoma and HeLa cells, (2) the information contained within 1.4 kb of 5'-flanking sequence is sufficient to confer its cell-specific expression, (3) the promoter responds to cAMP induction, and (4) the expression of the 5-HT transporter gene is regulated by a combination of positive and negative cis-acting elements operating through a basal promoter unit defined by a TATA-like motif.

Amino Acid Sequence

[Quantitative computerized tomography of the lung--respiration controlled diagnosis of diffuse lung diseases].

STUDY OBJECTIVE: Computed tomography provides measurements of lung attenuation which reflect changes in the air to tissue ratio and can thereby be employed for diagnosis of diffuse lung disease. In this prospective study, we quantitatively analyzed lung density by high resolution computed tomography (HRCT) in 26 healthy volunteers, 15 patients with chronic obstructive pulmonary disease (COPD), and 15 patients with idiopathic lung fibrosis (IPF). The procedure was standardized by examination of 3 scans at the carina +/- 5 cm and by defining inflation levels by %VC using an on-line hand held spirometer. RESULTS: Performance of HRCT at 50% VC provides not only significant and distinguishable group data, but is the easiest to carry out for dyspneic patients. The mean lung density at 50% VC for healthy subjects was -820 +/- 4.2 (mean +/- SEM) Hounsfield units (HU). It was significantly lower (p < 0.01) in COPD patients (-865 +/- 9.2 HU), and considerably higher (-697 +/- 17.8 HU, p < 0.001) in the IPF group. At an inflation level of 20% VC, mean lung density values were similarly distributed, at significantly lower values relative to those at 50% VC, but the procedure was more difficult to perform for patients with dyspnea. In contrast, at 80% VC, lung density values for the COPD and control groups were not significantly different (p = 0.08). The sensitivity to detect COPD was improved by selecting HRCT values lower than -900 HU, which represent the part of the lung with an increased air/tissue ratio. For IPF patients an increase of lung density values above -699 HU was characteristic, indicating a decrease of the air/tissue relationship. CONCLUSION: From our data we propose to perform quantitative HRCT measurements at 50% VC. Diagnosis of diffuse lung disease can be further improved by consideration of specific CT -value intervals. Spirometrically controlled quantitative HRCT is a clinically meaningful tool for the assessment of diffuse parenchymal lung disease.

Adult

Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation.

Coxsackievirus B3-induced myocarditis in different immunocompetent mouse strains was used as a model to investigate interrelationships between virus replication and development of chronic enteroviral heart disease. Using in situ hybridization to detect enteroviral RNA, we show that heart muscle infection is not only detected in acute myocarditis but is also detected during the chronic phase of the disease. Coxsackievirus B3 could evade immunological surveillance in a host-dependent fashion, thus inducing a persistent infection of the myocardium in association with ongoing inflammation. Patterns of acute and persistent myocardial infection were quantitatively assessed in one representative mouse strain (A.CA/SnJ, H-2f) by applying computer-assisted digital image processing; these patterns were then related to the extent of myocardial tissue damage as well as to inflammation. We observed a strong correlation, both spatial and temporal, between viral replication and development of myocardial lesions, indicating that acute and chronic myocardial injuries are a consequence of multifocal organ infection. Analysis of strand-specific in situ hybridization revealed that viral replication in persistent infection is restricted at the level of RNA synthesis. The described procedure for quantitating organ infection provides a powerful tool for evaluating virus-host interactions and will be of particular interest to those studying human enterovirus-induced cardiomyopathies.

Acute Disease

Natural history of Coxsackievirus B3-induced myocarditis in ACA/Sn mice: viral persistence demonstrated by quantitative in situ hybridization histochemistry.

Enteroviruses are considered to be the major aetiological agents of myocarditis in humans. Recent in situ hybridization studies on endomyocardial biopsies and autopsy hearts indicate that enterovirus RNA can be detected (pattern of persistent infection) not only in acute myocarditis (pattern of acute infection), but also in chronic dilated cardiomyopathy. Our experimental studies on murine coxsackievirus B3 myocarditis provided evidence that persistent infection may also occur in mice. Quantitative in situ hybridization and immunohistochemistry as well as electron microscopical in situ hybridization experiments were performed on ACA/SnJ mice 3-30 days after infection. The pattern of acute infection (days 3-9 p.i.) is characterized by rapid progression of myocardial lesions, an increasing number of inflammatory cells and a high number of infected myocytes. Hallmarks of the persistent pattern (days 15-30 p.i.) are reduced inflammation, reduced numbers of persistently infected cells and a slow progression of myocardial lesions. Infection is primarily restricted to degenerated, atrophic myocytes and to fibroblasts.

Animals

[Patterns of acute and persistent infections in enteroviral heart diseases].

Enteroviruses are considered as the major etiologic agents of myocarditis in humans. Recent in situ hybridization studies on endomyocardial biopsies indicate that not only in acute myocarditis (pattern of acute infection), but also in chronic dilated cardiomyopathy enterovirus RNA can be detected (pattern of persistent infection). Our experimental studies on murine coxsackievirus B3 myocarditis provided evidence that persistent infection occurs also in mice. Quantitative in-situ hybridization and immunohistochemistry as well as electron microscopic in situ hybridization experiments were performed on ACA/SnJ mice three to thirty days after infection. The pattern of acute infection (days 3-9 p.i.) is characterized by rapid progression of myocardial lesions, an increasing number of inflammatory cells and a high number of infected myocytes. Hallmarks of the persistent pattern (day 15-30 p.i.) are reduced inflammation, reduced numbers of persistently infected cells and a slow progression of myocardial lesions. Infection is primarily restricted to degenerated, atrophic myocytes and to fibroblasts.

Acute Disease

Spirometrically controlled quantitative CT for assessing diffuse parenchymal lung disease.

OBJECTIVE: Assessment of lung attenuation by CT reflects changes in the air-to-tissue ratio of the lung. We have analyzed the interdependence of intrathoracic gas volume, lung morphology, and functional disorder by high resolution CT (HRCT) to assess quantitative disease threshold in obstructive and restrictive diffuse lung disease. MATERIALS AND METHODS: Pulmonary HRCT was performed on 24 healthy volunteers, 11 patients with chronic obstructive pulmonary disease (COPD), and 16 patients with idiopathic lung fibrosis (IPF). HRCT measurement was standardized by taking three scans at the carina +/- 5 cm and by defining inspiration levels by percent vital capacity (VC) via spirometrically gating to the scanner. RESULTS: The mean lung density at 50% VC (DL50) for healthy subjects was -819 +/- 3.8 (mean +/- SEM) HU. In contrast, COPD DL50 was lower, averaging -861 +/- 6.4 HU, and the IPF DL50 was considerably higher (-731 +/- 17.7 HU), both significantly different (p < 0.001) compared with the control group. The accuracy of quantitative HRCT at different inspiration levels was evaluated by scanning the basal layer at 20, 50, and 80% VC. The control values were -747 +/- 5.6, -816 +/- 3.6, and -855 +/- 3.0 HU, respectively, which were significantly higher (p < 0.001) than those seen in COPD patients at 20 and 50% VC. Again, the IPF patients exhibited increased lung density (p < 0.001) at all inspiratory levels. Discrimination power was best among all cohorts at 20 and 50% VC. Position-dependent artifacts on lung density were quantified by the anteroposterior density gradient (APG). Irrespective of the underlying disease, APG at 50 and 80% VC was similar, but was up to twofold higher at 20% VC, indicating that quantitative estimates near RV may misrepresent mean lung density. CONCLUSION: Our data indicate that quantitative HRCT measurements should be performed not near full inspiration or expiration, but at an intermediate degree of lung inflation, e.g., 50% VC, for reasons of accuracy, intra- and intersubjective comparability, and feasibility. We conclude quantitative HRCT to be a sensitive tool for the evaluation of diffuse parenchymal lung disease.

Adult