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Biomedical subjects

D Hahn

Publications and source records attributed to D Hahn.

At least 145 records · Page 8Linked to original sources
PubMed1998

[3-dimensional MR coronary angiography with navigator technique: imaging of the proximal course of a coronary artery anomaly].

Congenital coronary artery anomalies are found in 0.3 to 1.3% of patients and can cause ischemic heart disease or sudden cardiac death, especially if the anomalous coronary artery courses between the aortic root and the pulmonary artery. Identification of the anatomic course of the anomalous vessel is not always feasible by conventional radiographic coronary angiography. With MR coronary angiography not only flowing blood but also the vessel anatomy can be imaged. In previous studies, a two-dimensional gradient-echo sequence during breathhold was used demanding both cooperation of the patient and operator skill. The navigator technique reduces respiratory artifacts by retrospective respiratory gating on the diaphragm's position, obviating the need for breathhold studies. Furthermore, the three-dimensional MR coronary angiography enables post-processing using the Volume Rendering Technique for evaluation of three-dimensional view. We report on the use of this technique for the identification of the course of anomalous coronary arteries in two patient cases.

Artifacts↗
PubMed1998

Invasion of cytotrophoblastic (JEG-3) cells is up-regulated by interleukin-15 in vitro.

PROBLEM: Trophoblast invasion into the uterus is controlled by many factors. Some cytokines (interleukin [IL]-1, IL-6, and IL-10) have been shown previously to play an important role in placentation. The human placenta is an important source of IL-15, although the cellular source of IL-15 in the placenta has not yet been specified. IL-15 influences cell adhesion and migration by redistributing adhesion molecules in lymphocytes and has been shown to have effects on endothelial cells and in some human tumors. METHOD OF STUDY: To study the role of IL-15 in trophoblast invasion, we investigated the effect of IL-15 (concentrations, 1-10 ng/ml) in a trophoblast invasion model (JEG-3 with matrigel-coated filters). Cell invasion was assessed using matrigel-coated filters and was expressed as the quotient of invading cells in comparison with the number of cells that had passed the control membrane. Cell migration was studied by examining the number of cells that had passed the filters without matrigel. Cell proliferation was quantified by a tetrazolium salt WST-1 cleavage assay. Matrix metalloproteinase (MMP)-1, MMP-2, and MMP-9 activities were measured by specific enzyme assays. RESULTS: IL-15 significantly (P < 0.05) increased the in vitro invasion of cytotrophoblastic (JEG-3) cells in a dose-dependent manner. There was a fourfold increase in the invasion at a concentration of 10 ng/ml of IL-15. Migration also was increased by a factor of 2.3 (P < 0.05). Cell proliferation, however, remained unchanged. The collagenolytic activity of cytotrophoblastic (JEG-3) cells was increased by IL-15 stimulation. A significant increase in MMP-1 concentration occurred after the incubation of JEG-3 cells with IL-15. No changes appeared in MMP-2, MMP-9, and tissue inhibitor of metalloproteinase-1 concentrations. CONCLUSIONS: Trophoblast invasion and migration, but not proliferation, are enhanced by IL-15. Our results suggest a role for IL-15 in the modulation of MMP-1 secretion by JEG-3 cells. Furthermore, we speculate, that IL-15 might be related to the changes of cell adhesion molecule phenotype during the process of invasion.

Cell Division↗
PubMed1998

Lymphadenopathy: differentiation of benign from malignant disease--color Doppler US assessment of intranodal angioarchitecture.

PURPOSE: To differentiate reactive from malignant lymphadenopathy by using color Doppler ultrasonographic (US) findings of intranodal blood vessels. MATERIALS AND METHODS: Color Doppler US was performed in 117 lymph nodes in 100 consecutive patients before performance of surgical biopsy (47 nodes), neck dissection (62 nodes), or high-speed core biopsy (eight nodes). The presence of malignant changes in intranodal angioarchitecture (focal perfusion defects, aberrant course of central vessels, displacement of intranodal vessels, subcapsular vessels) was evaluated in each node. Inter- and intraobserver variability were evaluated. RESULTS: Histopathologic examination demonstrated 48 reactive lymph nodes (longest diameter +/- standard deviation, 13.5 mm +/- 6.0), 56 nodal metastases (longest diameter, 19.2 mm +/- 8.8), 12 malignant lymphomas (longest diameter, 23.2 mm +/- 10.5), and one node infiltrated by Langerhans cell histiocytosis. At color Doppler US, 103 (88%) nodes were classified correctly, with a specificity of 77% and a sensitivity of 96%. Reproducibility was 90%-96% (kappa = 0.79-0.91, P < .001). CONCLUSION: Color Doppler US is a reliable and reproducible method for help in the differentiation between reactive and malignant alterations of superficial lymph nodes by using findings of intranodal angioarchitecture.

Adolescent↗
PubMed1998

Clinical cardiac magnetic resonance spectroscopy--present state and future directions.

MR spectroscopy opens a window to the non-invasive evaluation of various aspects of cardiac metabolism. Experimentally, the method has extensively been used since 1970's. 31P-MR allows the registration of cardiac high-energy phosphate metabolism to non-invasively estimate the energetic state of the heart: ATP, phosphocreatine, inorganic phosphate, monophosphate esters and intracellular pH can all be quantitated. In conjunction with extracellular shift reagents such as [DyTTHA]3- or [TmDOTP]5-, 23Na- and 39K-MR allow the measurement of intra- and extra-cellular cation pools. 1H-MR spectroscopy allows the detection of a large number of metabolites such as, e.g. creatine, lactate, or carnitine. Human cardiac spectrocsopy has so far been confined to the 31P nucleus. Localization techniques (DRESS, ISIS, 3D-CSI etc.) are required to confine the acquired signal to the heart region. Relative quantification is straightforward (phosphocreatine/ATP ratio), absolute quantification (mM) is under development. Cardiac 31P-MR spectroscopy has research application in at least three clinical areas: (1) Coronary artery disease: A biochemical stress test for non-invasive ischemia detection (decrease of phosphocreatine with exercise) and viability assessment via quantification of ATP may become feasible. (2) Heart failure: The phosphocreatine/ATP ratio may provide an independent index for grading of heart failure, allow to monitor the longterm effects of different forms of drug therapy on cardiac energy metabolism in heart failure, and may also hold prognostic information on survival. (3) Valve disease: It is possible that the decrease of phosphocreatine/ATP can be used to guide the timing for the valve replacement. At the present time, no routine clinical applications can be defined for the use of human cardiac spectroscopy in patients with cardiac disease. However, the technique holds great potential for the future as a non-invasive approach to cardiac metabolism, and in coming years routine applications may become reality.

Adenosine Triphosphate↗
PubMed1998

[The stepchild of intestinal diagnosis. Evaluation of radiologic methods in the diagnosis of leiomyoma of the small intestine].

PURPOSE: Various radiological methods to diagnose small bowel neoplasms and problems of differential diagnosis specially considering leiomyomas are discussed. PATIENTS AND METHODS: Two patients with leiomyoma of the ileum underwent enteroclysis, computed tomography of the abdomen, intra-arterial DSA and colour Doppler sonography. Another patient with leiomyosarcoma just underwent CT of the abdomen with CT-guided biopsy. RESULTS: Due to the homogenous density and the smooth surface of the tumors in computed tomography and respectively enteroclysis and the presentation of the tumor vascularisation in the angiography and Colour Doppler sonography in both patients a leiomyoma of the small bowel was diagnosed. Postoperatively this diagnosis was histologically confirmed. The CT-findings of the patient with leiomyosarcoma were not suspicious of a malignant tumor. CONCLUSION: Radiologically it is not possible to determine the dignity of smooth muscle cell tumors safely. That is the reason why the diagnosis has to be achieved operatively. But the histopathological diagnosis based on the mitotic rate may be difficult. Therefore the after care has to be carried out thoroughly.

Aged↗
PubMed1997

Myocardial phosphocreatine-to-ATP ratio is a predictor of mortality in patients with dilated cardiomyopathy.

BACKGROUND: In patients with heart failure due to dilated cardiomyopathy, cardiac energy metabolism is impaired, as indicated by a reduction of the myocardial phosphocreatine-to-ATP ratio, measured noninvasively by 31P-MR spectroscopy. The purpose of this study was to test whether the phosphocreatine-to-ATP ratio also offers prognostic information in terms of mortality prediction as well as how this index compares with well-known mortality predictors such as left ventricular ejection fraction (LVEF) or New York Heart Association (NYHA) class. METHODS AND RESULTS: Thirty-nine patients with dilated cardiomyopathy were followed up for 928+/-85 days (2.5 years). At study entry, LVEF and NYHA class were determined, and the cardiac phosphocreatine-to-ATP ratio was measured by localized 31P-MR spectroscopy of the anterior myocardium. During the study period, total mortality was 26%. Patients were divided into two groups, one with a normal phosphocreatine-to-ATP ratio (>1.60; mean+/-SE, 1.98+/-0.07; n=19; healthy volunteers: 1.94+/-0.11, n=30) and one with a reduced phosphocreatine-to-ATP ratio (<1.60; 1.30+/-0.05; n=20). At re-evaluation (mean, 2.5 years), 8 of 20 patients with reduced phosphocreatine-to-ATP ratios had died, all of cardiovascular causes (total and cardiovascular mortality, 40%). Of the 19 patients with normal phosphocreatine-to-ATP ratios, 2 had died (total mortality, 11%), one of cardiovascular causes (cardiovascular mortality, 5%). Kaplan-Meier analysis showed significantly reduced total (P=.036) and cardiovascular (P=.016) mortality for patients with normal versus patients with low phosphocreatine-to-ATP ratios. A Cox model for multivariate analysis showed that the phosphocreatine-to-ATP ratio and NYHA class offered significant independent prognostic information on cardiovascular mortality. CONCLUSIONS: The myocardial phosphocreatine-to-ATP ratio, measured noninvasively with 31P-MR spectroscopy, is a predictor of both total and cardiovascular mortality in patients with dilated cardiomyopathy.

Adenosine Triphosphate↗
PubMed1997

Polarised expression of human intestinal N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase (human meprin) alpha and beta subunits in Madin-Darby canine kidney cells.

N-Benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase (PPH, human meprin), is a peptidase found in the microvillus membrane of human small intestinal epithelial cells. PPH belongs to the astacin family of zinc-metalloendopeptidases and is a protein complex composed of two glycosylated subunits, alpha and beta. The present report describes the cloning of the complete beta subunit and the remaining N2-terminal end of the alpha subunit for analysis of their primary structures in addition to the examination of their biogenesis in transfected cell cultures. The complete open reading frame of the PPH beta cDNA translates into 700 amino acid residues compared with 746 residues for the PPH alpha cDNA. The primary structure of beta and alpha subunits are 44% identical and 61% similar. As predicted from their primary structure, the two subunits of PPH have identical modular structures; starting at the N2-terminus both contain a signal peptide, a propeptide, a protease domain containing the astacin signature, a meprin A5 protein tyrosine phospatase mu (MAM) and a meprin and TRAF homology domain (MATH) domain, an epidermal growth factor(EGF)-like domain, a putative transmembrane anchor domain and a short cytosolic tail. Pulse/chase labelling and immuno-Gold electronmicroscopy of recombinant PPH beta and alpha subunits expressed in transfected Madin-Darby canine kidney (MDCK) cells show that post-translational processing and transport of the two subunits are very different. When expressed alone, the beta subunit acquired complex glycan residues, readily formed homodimers and was transported to the plasma membrane. Small amounts of PPH beta were found in the culture medium. In contrast, the cell-bound alpha subunit, when expressed alone, remained primarily in the high-mannose form, was aggregated and not expressed at the cell surface. However, the bulk of mostly endo-beta-N-acetylglucosaminidase H-resistant alpha subunit was found in the filtered culture medium. The proteolytic event that leads to the formation of this soluble transport-competent form occurs in the endoplasmic reticulum (ER). Coexpression of the alpha subunit with the beta subunit allowed the localisation of the alpha subunit to the plasma membrane. These studies indicate that assembly of the two subunits of PPH is required for the localisation of the alpha subunit to the plasma membrane. In contrast to rodent meprin, both PPH subunits are apically secreted from MDCK cells.

Amino Acid Sequence↗
PubMed1997

C-cytosolic and transmembrane domains of the N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase alpha subunit (human meprin alpha) are essential for its retention in the endoplasmic reticulum and C-terminal processing.

N-benzoyl-L-tyrosyl-p-aminobenzoic acid hydrolase (PPH, human meprin) is a member of the astacin family of Zn-metalloendopeptidases and is highly expressed in the microvillus membrane of human small intestinal epithelial cells. It is a type I transmembrane protein consisting of differentially processed glycosylated alpha and beta subunits. Biosynthesis experiments using transfected, metabolically labelled simian virus 40 (SV40) transformed african green monkey kidney cells (COS-1) and Madin Darby canine kidney (MDCK) cells, have previously shown that PPH alpha was retained in the endoplasmic reticulum (ER) and that for subsequent secretion removal of the alpha-tail was necessary [Grünberg, J., Dumermuth, E., Eldering, J. A. & Sterchi, E. E. (1993) FEBS Lett. 335, 376-379]. We proposed an involvement of the alpha-tail in ER retention. To investigate the possible role of the transmembrane and/or the C-terminal domain of the alpha-subunit, tailswitch mutants were constructed in which these domains were exchanged between the alpha and beta subunits. Biosynthesis and post-translational processing of these mutants were investigated in transiently transfected COS-1 cells. The beta/alpha tailswitch mutant, in which the transmembrane and C-cytosolic parts of PPH beta were substituted by the corresponding parts of the PPH alpha subunit, was transported much slower compared with the wild-type PPH beta subunit. In addition, fusion of the alpha-tail to a C-terminally truncated secretory form of PPH alpha leads to its retention in the ER. This mutant, but not the secretory form, coimmunoprecipitated with calnexin, indicating an involvement of this molecular chaperone in retaining PPH alpha in the ER. The alpha/beta tailswitch mutant, in which the transmembrane domain and the C-cytosolic part of PPH alpha were substituted by the corresponding parts of PPH beta, was processed less efficiently in comparison with PPH alpha, resulting in a lower secretion rate. Taken together these data suggest a role of the alpha-tail in mediating association with ER-resident machinery, facilitating C-terminal processing.

Animals↗
PubMed1997

Expression of CD44 isoforms by highly enriched CD34-positive cells in cord blood, bone marrow and leukaphereses.

CD34-positive cells were isolated from cord blood (n = 8), bone marrow (n = 4) and leukapheresed material (n = 7), using an immunomagnetic isolation technique, MACS (Miltenyi Biotec, Bergisch Gladbach, Germany). In flow cytometric analysis, cell populations after enrichment revealed a fraction of 96.1% (cord blood), 96.2% (bone marrow) and 98.6% (leukapheresis material) CD34-positive cells. Cells were further stained with antibodies specific for CD44 isoforms: CD44s (SFF-2), CD44v5 (VFF-8) and CD44v6 (VFF-18). CD44-positive cells were detected by directly (FITC, fluorescein isothiocyanate) or indirectly (streptavidin-PE, phycoerythrin)-conjugated fluorochromes in flow cytometric analysis. Analysis was restricted to CD34-positive cells. A high expression of CD44s was noted in all kinds of material under investigation with mean values in the range of 98.6-100%. There was little expression of CD44v6 (mean values in the range of 1.5-3.6%) and very slight expression of CD44v5 (mean values in the range of 0.6-1.4%). The finding that CD34-positive hematopoietic stem cells express CD44v5 and CD44v6 to a very small extent offers the possibility of using antibodies specific to CD44v5 and CD44v6 in immunopurging in the course of autologous stem cell transplantation.

Adult↗
PubMed1997

[Use of a PACS for ultrasound connection].

PURPOSE: This report describes the impact of a new digital picture archiving and communication system-PACS-in a diagnostic ultrasound department. The system consists of ultrasound workstations, a patient management workstation, a combined diagnostic workstation/archive server and a WWW client for standard PCs. Data exchange with other PAC-systems is possible via Ethernet. Staff required approximately 5 weeks to fully adjust to the new system. Following the adjustment period, documenting cases digitally reduced our exam times and improved our availability of images and reports for subsequent examinations, demonstrations, research and teaching. In the first year after installation, the new ultrasound PACS has proven its value in daily use.

Evaluation Studies as Topic↗
PubMed1997

In situ analysis of denitrifying toluene- and m-xylene-degrading bacteria in a diesel fuel-contaminated laboratory aquifer column.

A diesel fuel-contaminated aquifer was bioremediated in situ by the injection of oxidants (O2 and NO3-) and nutrients in order to stimulate microbial activity. After 3.5 years of remediation, an aquifer sample was excavated and the material was used (i) to isolate bacterial strains able to grow on selected hydrocarbons under denitrifying conditions and (ii) to construct a laboratory aquifer column in order to simulate the aerobic and denitrifying remediation processes. Five bacterial strains isolated from the aquifer sample were able to grow on toluene (strains T2 to T4, T6, and T10), and nine bacterial strains grew on toluene and m-xylene (strains M3 to M7 and M9 to M12). Strains T2 to T4, T6, and T10 were cocci, and strains M3 to M7 and M9 to M12 were rods. The morphological and physiological differences were also reflected in small sequence variabilities in domain III of the 23S rRNA and in the 16S rRNA. Comparative sequence analyses of the 16S rRNA of one isolate (T3 and M3) of each group revealed a close phylogenetic relationship for both groups of isolates to organisms of the genus Azoarcus. Two 16S rRNA-targeted oligonucleotide probes (Azo644 and Azo1251) targeting the experimental isolates, bacteria of the Azoarcus tolulyticus group, and Azoarcus evansii were used to investigate the significance of hydrocarbon-degrading Azoarcus spp. in the laboratory aquifer column. The number of bacteria in the column determined after DAPI (4',6-diamidino-2-phenylindole) staining was 5.8 x 10(8) to 1.1 x 10(9) cells g of aquifer material-1. About 1% (in the anaerobic zone of the column) to 2% (in the aerobic zone of the column) of these bacteria were detectable by using a combination of probes Azo644 and Azo1251, demonstrating that hydrocarbon-degrading Azoarcus spp. are significant members of the indigenous microbiota. More than 90% of the total number of bacteria were detectable by using probes targeting higher phylogenetic groups. Approximately 80% of these bacteria belonged to the beta subdivision of the class Proteobacteria (beta-Proteobacteria), and 10 to 16% belonged to the gamma-Proteobacteria. Bacteria of the alpha-Proteobacteria were present in high numbers (10%) only in the aerobic zone of the column.

Bacteria↗
PubMed1997

[Massive hemorrhage from jejunal varices].

A 21-year-old male presented with melaena and signs of hemorrhagic shock. In the following days several episodes of hematochezia occurred requiring the transfusion of nine units of blood. Findings at gastroscopy were normal, at colonoscopy fresh blood was noted from the ileocecal valve. Angiography performed in a bleeding-free interval showed no abnormalities. At repeat angiography, bleeding (from a left lateral branch of the superior mesenteric artery) was provoked by instillation of plasminogen activator. Subsequently, hemostasis was achieved by superselective embolization using coils. At operation one week later, a polypoid tumor of 1 cm diameter was resected along with a 4 cm segment of adjacent jejunum (40 cm distal to the ligament of Treitz). Histologically, a jejunal varix with superficial ulceration was diagnosed.

Adult↗
PubMed1997

Cardiac high-energy phosphate metabolism in patients with aortic valve disease assessed by 31P-magnetic resonance spectroscopy.

BACKGROUND: The purpose of this work was to determine the clinical and hemodynamic correlates of alterations in cardiac high-energy phosphate metabolism in patients with aortic stenosis and with aortic incompetence. METHODS: Fourteen volunteers, 13 patients with aortic stenosis, and 9 patients with aortic incompetence were included. Patients underwent echocardiography and left and right heart catheterization. 31P-MR spectra from the anterior myocardium were obtained with a 1.5 Tesla clinical MR system. RESULTS: Aortic stenosis and aortic incompetence patients had similar New York Heart Association (NYHA) classes (2.77 +/- 0.12 vs 2.44 +/- 0.18), ejection fractions (normal), left ventricular (LV) end-diastolic pressures, and LV wall thickness. In volunteers, phosphocreatine/adenosine triphosphate (ATP) ratios were 2.02 +/- 0.11. For all patients, phosphocreatine/ATP was significantly reduced (1.64 +/- 0.09; *p = 0.011 vs volunteers). Phosphocreatine/ATP decreased to 1.55 +/- 0.12 (*p = 0.008) in aortic stenosis, while in aortic incompetence, phosphocreatine/ATP only showed a trend for a reduction (1.77 +/- 0.12; p = 0.148). For all patients, phosphocreatine/ATP decreased significantly only with NYHA class III (1.51 +/- 0.09; *p = 0.001), but not with NYHA classes I and II (phosphocreatine/ATP 1.86 +/- 0.18). In aortic stenosis, phosphocreatine/ATP ratios decreased (1.13 +/- 0.03; *p = 0.019) only when LV end-diastolic pressures were > 15 mm Hg or when LV diastolic wall stress was > 20 kdyne cm-2 (1.13 +/- 0.03; *p = 0.024). CONCLUSIONS: For a similar clinical degree of heart failure in human myocardium, volume overload hypertrophy does not, but pressure overload does, induce significant impairment of cardiac high-energy phosphate metabolism. In aortic valve disease, alterations of high-energy phosphate metabolism are related to the degree of heart failure.

Adenosine Triphosphate↗
PubMed1996

Proteolytic processing of human lactase-phlorizin hydrolase is a two-step event: identification of the cleavage sites.

Human lactase-phlorizin hydrolase (EC 3.2.1.23/62) is a major disaccharidase in the microvillus membrane of small intestinal epithelial cells. The enzyme is synthesized as a single-chain precursor protein and undergoes proteolytic processing during maturation. We studied proteolytic processing of human lactase-phlorizin hydrolase in transfected COS-1, Caco-2, and MDCK cells using metabolic labeling, surface immunoprecipitation, protease sensitivity assays, and microsequencing. Furthermore, we generated mutated forms of the enzyme to alter potential proteolytic cleavage sites and expressed these in Caco-2 and COS-1 cells. Since the N-terminal amino acid of microvillus lactase-phlorizin hydrolase corresponds to Ala869 in the precursor protein, it has been speculated that processing occurs at position Arg868-Ala869. Substitution of Arg868 with isoleucine, lysine, or glutamic acid had no effect on the proteolytic processing of pro-LPH in Caco-2 cells. As in wild-type enzyme a processed 160-kDa form was generated. These data are not consistent with a primary proteolytic processing at position Arg868-Ala869. Using amino-terminal amino acid sequencing of this processed form isolated from stable transfected MDCK cells we identified the cleavage site at Arg734-Leu735. Treatment of pro-lactase-phlorizin hydrolase expressed in COS-1 and MDCK cells by trypsin yielded a 145-kDa form with an identical amino terminal as the mature microvillus enzyme isolated from intestinal mucosa (Ala869). These data provide unambiguous evidence of a two-step processing of human lactase-phlorizin hydrolase. The first cleavage occurs intracellularly after a dibasic site (Arg734-Leu735) and yields the 160-kDa intermediate form. In a second step the intermediate form inserted into the microvillus membrane is trimmed to the mature enzyme by luminal trypsin.

Animals↗