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S Buchner

Publications and source records attributed to S Buchner.

At least 19 recordsLinked to original sources
PubMed2006

Delayed hyperenhancement in magnetic resonance imaging of left ventricular hypertrophy caused by aortic stenosis and hypertrophic cardiomyopathy: visualisation of focal fibrosis.

OBJECTIVE: To compare the extent and distribution of focal fibrosis by gadolinium contrast-enhanced magnetic resonance imaging (MRI; delayed hyperenhancement) in severe left ventricular (LV) hypertrophy in patients with pressure overload caused by aortic stenosis (AS) and with genetically determined hypertrophic cardiomyopathy (HCM). METHODS: 44 patients with symptomatic valvular AS (n = 22) and HCM (n = 22) were studied. Cine images were acquired with fast imaging with steady-state precession (trueFISP) on a 1.5 T scanner (Sonata, Siemens Medical Solutions). Gadolinium contrast-enhanced MRI was performed with a segmented inversion-recovery sequence. The location, extent and enhancement pattern of hyperenhanced myocardium was analysed in a 12-segment model. RESULTS: Mean LV mass was 238.6 (SD 75.3) g in AS and 205.4 (SD 80.5) g in HCM (p = 0.17). Hyperenhancement was observed in 27% of patients with AS and in 73% of patients with HCM (p < 0.01). In AS, hyperenhancement was observed in 60% of patients with a maximum diastolic wall thickness >or= 18 mm, whereas no patient with a maximum diastolic wall thickness < 18 mm had hyperenhancement (p < 0.05). Patients with hyperenhancement had more severe AS than patients without hyperenhancement (aortic valve area 0.80 (0.09) cm(2)v 0.99 (0.3) cm(2), p < 0.05; maximum gradient 98 (22) mm Hg v 74 (24) mm Hg, p < 0.05). In HCM, hyperenhancement was predominant in the anteroseptal regions and patients with hyperenhancement had higher end diastolic (125.4 (36.9) ml v 98.8 (16.9) ml, p < 0.05) and end systolic volumes (38.9 (18.2) ml v 25.2 (1.7) ml, p < 0.05). The volume of hyperenhancement (percentage of total LV myocardium), where present, was lower in AS than in HCM (4.3 (1.9)% v 8.6 (7.4)%, p< 0.05). Hyperenhancement was observed in 4.5 (3.1) and 4.6 (2.7) segments in AS and HCM, respectively (p = 0.93), and the enhancement pattern was mostly patchy with multiple foci. CONCLUSIONS: Focal scarring can be observed in severe LV hypertrophy caused by AS and HCM, and correlates with the severity of LV remodelling. However, focal scarring is significantly less prevalent in adaptive LV hypertrophy caused by AS than in genetically determined HCM.

Aortic Valve Stenosis↗
PubMed2006

MRI planimetry for diagnosis and follow-up of valve area in mitral stenosis treated with valvuloplasty.

PURPOSE: We sought to determine whether noninvasive planimetry by magnetic resonance imaging (MRI) is suitably sensitive and reliable for visualizing the mitral valve area (MVA) and for detecting increases in the MVA after percutaneous balloon mitral valvuloplasty (PBMV). MATERIALS AND METHODS: In 8 patients with mitral valve stenosis, planimetry of the MVA was performed before and after PBMV with a 1.5 T MR scanner using a breath-hold balanced gradient echo sequence (True FISP). The data was compared to the echocardiographically determined MVA (ECHO-MVA) as well as to the invasively calculated MVA by the Gorlin formula at catheterization (CATH-MVA). RESULTS: PBMV was associated with an increase of 0.79 +/- 0.30 cm (2) in the MVA (Delta MRI-MVA). The correlation between Delta MRI-MVA and Delta CATH-MVA was 0.92 (p < 0.03) and that between Delta MRI-MVA and Delta ECHO-MVA was 0.90 (p < 0.04). The overall correlation between MRI-MVA and CATH-MVA was 0.95 (p < 0.0001) and that between MRI-MVA and ECHO-MVA was 0.98 (p < 0.0001). MRI-MVA slightly overestimated CATH-MVA by 8.0 % (1.64 +/- 0.45 vs. 1.51 +/- 0.49 cm (2), p < 0.01) and ECHO-MVA by 1.8 % (1.64 +/- 0.45 vs. 1.61 +/- 0.43 cm (2), n. s.). CONCLUSION: Magnetic resonance planimetry of the mitral valve orifice is a sensitive and reliable method for the noninvasive quantification of mitral stenosis and visualization of small relative changes in the MVA. This new method is therefore capable of diagnosing as well as following the course of mitral stenosis. It must be taken into consideration that planimetry by MRI slightly overestimates the MVA as compared to cardiac catheterization.

Anatomy, Cross-Sectional↗
PubMed2005

NT-ProBNP in outpatients after myocardial infarction: interaction between symptoms and left ventricular function and optimized cut-points.

BACKGROUND: N-terminal pro-brain natriuretic peptide (NT-proBNP) allows us to rule out left ventricular dysfunction (LVD) in the general population at a recommended cut-off concentration of 125 pg/mL. It was our objective to reassess this cut-point in outpatients after myocardial infarction. METHODS AND RESULTS: NT-proBNP was assessed in 418 randomly selected outpatients who had experienced myocardial infarction and 352 siblings who had not experienced myocardial infarction (control). Left ventricular ejection fraction (LVEF) and mass-index (LVMI) were assessed by echocardiography. NT-proBNP was elevated in outpatients after myocardial infarction (mean [+/-SEM], 305 +/- 25 pg/mL vs control, 84 +/- 8 pg/mL; P < .01) and was correlated inversely with LVEF ( P < .001). When patients were stratified according to the presence or absence of heart failure, NT-proBNP was elevated significantly throughout all LVEF strata (each P < .05). On regression analysis, NT-proBNP was correlated independently with LVEF, LVMI, heart failure, and glomerular filtration rate (all P < .01). In patients with heart failure, the optimal cut-point for the detection of an LVEF <35% was 348 pg/mL (sensitivity 80%; specificity 69%) and for the detection of an LVEF <45% was 260 pg/mL (sensitivity 60%; specificity 60%). The relative risk for LVD in the presence of elevated NT-proBNP increased from 2.7 to 7.7 (EF < 35%) and from 1.4 to 2.4 (EF < 45%) when these cut-points were applied instead of the 125 pg/mL cut-point. An LVEF of <35% could be ruled out in symptomatic outpatients after myocardial infarction with a negative predictive value of 97% (cut-point 348 pg/mL) and in asymptomatic outpatients after myocardial infarction with a negative predictive value of 98% (cut-point 157 pg/mL). CONCLUSION: NT-proBNP is higher in outpatients after myocardial infarction than in the general population. In symptomatic patients, a cut-point of 348 pg/mL yields satisfactory sensitivity and specificity for the detection of significant LVD (EF < 35%). Furthermore, significant LVD can be virtually ruled out in symptomatic and asymptomatic outpatients after myocardial infarction at below-threshold concentrations.

Aged↗
PubMed2002

Quantitative analysis of energy metabolism in human muscle using SLOOP 31P-MR-spectroscopy.

OBJECTIVE: Energy metabolism is vital for regular muscle function. In humans, in-vivo analysis using (31)P-MR-spectroscopy (MRS) is mostly restricted to semiquantitative parameters due to technical demands. We applied Spatial Localization with Optimal Pointspread Function (SLOOP) for quantification in human skeletal and cardiac muscle. SUBJECTS/METHODS: 10 healthy volunteers and 4 patients with myotonic dystrophy type 1 were examined using a 1.5 T system (Magnetom VISION) and chemical shift imaging (CSI) for data collection. Concentrations of PCr, ATP and Pi as well as PCr/ATP ratios were calculated by SLOOP. RESULTS: Concentrations of PCr, ATP and Pi were 29.9 +/- 3.4, 7.1 +/- 0.9 and 5.7 +/- 1.2 [mmol/kg] in normal skeletal muscle, corresponding to previously published studies. Two of the patients with a duration of disease longer than 10 years and a pronounced muscle weakness showed a significant decrease of PCr and ATP in skeletal muscle below 10 and 5 mmol/kg. One of these patients had an additional reduction of PCr in cardiac muscle. CONCLUSIONS: With MRS and SLOOP, a more accurate quantitative assessment of metabolism is now available in skeletal and cardiac muscle. Longitudinal studies of larger patient groups will allow to better describe the metabolic disorder in muscle disease over time. Moreover, these techniques offer a new way to quantify treatment effects in future trials.

Adult↗
PubMed2001

The black-pearl gene of Drosophila defines a novel conserved protein family and is required for larval growth and survival.

Using a transposon insertion line of the Drosophila Genome Project we have cloned the black-pearl gene (blp), analyzed cDNA clones, generated various mutants, and characterized their phenotypes. The blp gene codes for a protein of 15.7 kDa calculated molecular weight that has been conserved from yeast to plants and mammals with high homology. A domain of these new proteins shows distant similarity to DnaJ domains indicating a functionally relevant interaction with other proteins. The P element insertion in line P1539 lies within the 5' untranslated leader of the black-pearl gene. Flies homozygous for this insertion are semi-lethal, escapers produce very few offspring and show melanotic inclusions in the hemocoel ('black pearls') similar to various melanotic 'tumor' mutants. Two small deletions confined to the blp gene and two EMS-induced mutations are homozygous lethal. These null mutants appear normal up to a prolonged first instar larval stage but fail to grow and die. Thus in Drosophila the blp gene is specifically required for larval growth. The evolutionary conservation in both unicellular and multicellular organisms suggests for the new protein family described here a fundamental role in cell growth.

5' Untranslated Regions↗
PubMed2001

(31)P-MR Spectroscopy for the evaluation of energy metabolism in intact residual myocardium after acute myocardial infarction in humans.

OBJECTIVE: Experimental studies have demonstrated that acute myocardial infarction (MI) alters energy metabolism even in non-infarcted adjacent tissue. In patients with subacute MI, the influence of the regional ischemic insult on energy metabolism of intact septal myocardium was analyzed using 31P-Magnetic resonance spectroscopy (MRS). PATIENTS AND METHODS: In eight patients with wall motion abnormalities in the anterior wall 31P-spectra were obtained from non-infarcted adjacent septal myocardium, as well as infarcted anterior myocardium (voxel size 25 ccm each) 29+/-8 days after MI using a 3D-CSI technique. Additionally, cardiac function was analyzed using breath-hold cine MRI. MRI was repeated 6 months after revascularization to assess viability of infarcted segments. Eight age-matched healthy volunteers served as control group. RESULTS: According to follow-up MRI 4/8 patients showed regional wall motion recovery. Here, PCr/ATP-ratios were not significantly reduced in intact septal myocardium as well as infarcted anterior myocardium compared to healthy volunteers (1.28+/-0.10 and 1.14+/-0.09 vs. 1.45+/-0.29). No recovery of regional function was detected in 4/8 patients with-therefore-non-viable anterior myocardium. PCr/ATP-ratios were significantly reduced in intact and infarcted myocardium compared with healthy volunteers as well as to patients with wall motion recovery (0.77+/-0.17 and 0.49+/-0.23; P<0.05). DISCUSSION: These preliminary results indicate that energy metabolism is reduced in patients with persisting wall motion abnormalities after myocardial infarction and revascularization in ischemically injured as well as in adjacent non-injured myocardium.

Aged↗
PubMed2001

Cardiac metabolism and function in patients with multiple sclerosis: a combined 31P-MR-spectroscopy and MRI study.

OBJECTIVE: Involvement of the autonomic system in multiple sclerosis (MS) may concur with dysfunction of the cardiovascular system. The introduction of potentially cardiotoxic immunosuppressive drugs like Mitoxantrone into the treatment of MS warrants proper assessment of preexisting heart disease. However, systematic analyses of functional and metabolic derangements in MS are missing. Using quantitative 31P-MR-spectroscopy (MRS) and MR-imaging (MRI) metabolic and functional parameters were analyzed in patients with MS in comparison to healthy volunteers. SUBJECTS/METHODS: 14/15 patients with MS could be included in the study, as the MRS examination of one patient had to be excluded from analysis due to movement during the examination. Using chemical shift imaging (CSI) and AMARES, phosphocreatine (PCr) to adenosine triphosphate (ATP) ratios, characterizing myocardial high-energy phosphate metabolism, were determined. Additionally, absolute concentrations of PCr and ATP were calculated by SLOOP (Spatial Localization with Optimal Pointspread Function). Analysis of functional changes was performed by Cine-MRI. 14 healthy volunteers matched for age and gender served as control. RESULTS: A significant decrease of absolute PCr concentration was observed in patients with MS compared to matched volunteers (p < 0.05), whereas ATP concentrations showed no significant changes (p = 0.27). Metabolite ratios calculated by SLOOP or AMARES showed a tendency to be reduced in patients, however, did not reach significance (p = 0.08, SLOOP; p = 0.47, AMARES). Using volunteers' mean values +/- 2 x SD as cut off value revealed PCr changes in 5 of 14 patients, whereas only 2 also had pathologic PCr/ATP ratios. Functional analysis by MRI depicted depressed left ventricular ejection fraction in 4 patients. CONCLUSIONS: The reduction in cardiac high-energy phosphates in some patients with MS points to a subclinical involvement of the heart. This may be important for treatment with potentially cardiotoxic drugs. Longitudinal studies are need to understand the clinical relevance of our findings.

Adenosine Triphosphate↗
PubMed2001

[31P-MR spectroscopy of all regions of the human heart at 1.5 T with acquisition-weighted chemical shift imaging].

AIM: Aim of this study was to show whether or not acquisition-weighted chemical shift imaging (AW-CSI) allows the determination of PCr and ATP in the lateral and posterior wall of the human heart at 1.5 T. METHODS: 12 healthy volunteers were examined using a conventional chemical shift imaging (CSI) and an AW-CSI. The sequences differed only in the number of repetitions for each point in k space. A hanning function was used as filter function leading to 7 repetitions in the center of the k space and 0 in the corners. Thus, AW-CSI had the same resolution as the CSI sequence. The results for both sequences were analyzed using identically positioned voxels in the septal, anterior, lateral and posterior wall. RESULTS: The determined averaged AW-CSI signal to noise ratios were higher for PCr by a factor of 1.3 and for ATP by 1.4 than those of CSI. The PCr/ATP ratios were higher by a factor of 1.2 - 1.3 and showed a smaller standard deviation in all locations for AW-CSI. The mean PCr/ATP ratios determined by AW-CSI of septal, lateral and posterior wall were almost identical (1.72 - 1.76), while it was higher in the anterior wall (1.9). CONCLUSIONS: The reduced contamination in AW-CSI improves the signal to noise ratio and the determination of the PCr/ATP ratio in cardiac (31)P spectroscopy compared to CSI with the same resolution. The results in volunteers indicate that AW-CSI renders (31)P spectroscopy of the lateral and posterior wall of the human heart feasible for patient studies at 1.5 T.

Adenosine Triphosphate↗
PubMed2000

Metastable states as a key to the dynamics of supercooled liquids

Computer simulations of a model glass-forming system are presented, which study the correlation between the dynamics in real space and the topography of the potential energy landscape. This analysis clearly reveals that in the supercooled regime the dynamics is strongly influenced by the presence of deep valleys in the energy landscape, corresponding to long-lived metastable amorphous states. We explicitly relate nonexponential relaxation effects and dynamic heterogeneities to these metastable states and thus to the specific topography of the energy landscape.

Journal Article↗
PubMed2000

Inflated wings, tissue autolysis and early death in tissue inhibitor of metalloproteinases mutants of Drosophila.

In vertebrates, tissue inhibitors of metalloproteinases (TIMPs) play key roles in extracellular matrix (ECM) homeostasis and growth control. Deletion of the recently cloned Timp gene of Drosophila results in a subviable phenotype. Adult flies display inflated wings similar to integrin mutants, suffer from a bloated gut and progressive dissolution of internal tissues, and die prematurely. Our results demonstrate that the Timp gene product controls selective aspects of ECM function in Drosophila, and suggest that it is involved in cell adhesion/cell signaling pathways. Hence, Drosophila Timp mutants may prove useful as a model system for a wide variety of pathological conditions related to ECM dysregulation.

Abdomen↗
PubMed1998

Wide distribution of the cysteine string proteins in Drosophila tissues revealed by targeted mutagenesis.

The "cysteine string protein" (CSP) genes of higher eukaryotes code for a novel family of proteins characterized by a "J" domain and an unusual cysteine-rich region. Previous studies had localized the proteins in neuropil and synaptic terminals of larval and adult Drosophila and linked the temperature-sensitive paralysis of the mutants described here to conditional failure of synaptic transmission. We now use the null mutants as negative controls in order to reliably detect even low concentrations of CSPs by immunohistochemistry, employing three monoclonal antibodies. In wild-type flies high levels of cysteine string proteins are found not only in apparently all synaptic terminals of the embryonic, larval, and adult nervous systems, but also in the "tall cells" of the cardia, in the follicle cells of the ovary, in specific structures of the female spermatheca, and in the male testis and ejaculatory bulb. In addition, low levels of CSPs appear to be present in all tissues examined, including neuronal perikarya, axons, muscles, Malpighian tubules, and salivary glands. Western blots of isolated tissues demonstrate that of the four isoforms expressed in heads only the largest is found in non-neural organs. The wide expression of CSPs suggests that at least some of the various phenotypes of the null mutants observed at permissive temperatures, such as delayed development, short adult lifespan, modified electroretinogram, and optomotor behavior, may be caused by the lack of CSPs outside synaptic terminals.

Age Factors↗
PubMed1996

Invertebrate synapsins: a single gene codes for several isoforms in Drosophila.

Vertebrate synapsins constitute a family of synaptic proteins that participate in the regulation of neurotransmitter release. Information on the presence of synapsin homologs in invertebrates has been inconclusive. We have now cloned a Drosophila gene coding for at least two inferred proteins that both contain a region with 50% amino acid identity to the highly conserved vesicle- and actin-binding "C" domain of vertebrate synapsins. Within the C domain coding sequence, the positions of two introns have been conserved exactly from fly to human. The positions of three additional introns within this domain are similar. The Drosophila synapsin gene (Syn) is widely expressed in the nervous system of the fly. The gene products are detected in all or nearly all conventional synaptic terminals. A single amber (UAG) stop codon terminates the open reading frame (ORF1) of the most abundant transcript of the Syn gene 140 amino acid codons downstream of the homology domain. Unexpectedly, the stop codon is followed by another 443 in-frame amino acid codons (ORF2). Using different antibodies directed against ORF1 or ORF2, we demonstrate that in the adult fly small and large synapsin isoforms are generated. The small isoforms are only recognized by antibodies against ORF1; the large isoforms bind both kinds of antibodies. We suggest that the large synapsin isoform in Drosophila may be generated by UAG read-through. Implications of such an unconventional mechanism for the generation of protein diversity from a single gene are discussed.

Amino Acid Sequence↗
PubMed1996

Genetic depletion of histamine from the nervous system of Drosophila eliminates specific visual and mechanosensory behavior.

The role of histamine as a fast neurotransmitter of imaginal insect photoreceptors is firmly established. In adult Drosophila, histamine is also found in mechanosensory receptors of cuticular hair sensilla and in a small number of nonreceptor neurons in head and body ganglia. Here we investigate the function of histamine by immunohistochemical and behavioral analysis of mutants deficient in the hdc gene that codes for histidine decarboxylase. The allele hdcJK910 appears to be a null mutation, as histamine immunoreactivity is almost entirely eliminated. Homozygous flies are blind in various behavioral paradigms. Mutant larvae, on the other hand, show normal photokinetic responses. Thus, adult Drosophila photoreceptors most likely utilize only a single substance, histamine, as a neurotransmitter, whereas larval photoreceptors apparently employ a different transmitter. With the alleles hdcP211, hdcP217, and hdcP218, variable amounts of histamine are found in photoreceptors and mechanoreceptors, but no histamine could be detected in any of the nonreceptor neurons. These mutants show various degrees of visual and mechanosensory impairment, as determined by quantitative behavioral assays. We conclude that histamine is required for normal function of cuticular hair sensilla and for efficient grooming of the body surface. Thus, in Drosophila, histamine represents a major functional neurotransmitter for mechanosensory receptors.

Animals↗
PubMed1993

Histamine is a major mechanosensory neurotransmitter candidate in Drosophila melanogaster.

Histamine is known to be the neurotransmitter of insect photoreceptors. Histamine-like immunoreactivity is also found in a number of interneurons in the central nervous system of various insects. Here, we demonstrate by immunohistochemical techniques that, in Drosophila melanogaster (Acalypterae), most or all mechanosensory neurons of imaginal hair sensilla selectively bind antibodies directed against histamine. The histamine-like staining includes the cell bodies of these neurons as well as their axons, which form prominent fibre bundles in peripheral nerves, and their terminal projections in the central neuropil of head and thoracic ganglia. The specificity of the immunostaining is demonstrated by investigating a Drosophila mutant unable to synthesize histamine. Other mechanosensory organs, such as campaniform sensilla or scolopidial organs, do not stain. In the calypteran flies, Musca and Calliphora, we find no comparable immunoreactivity associated with either hair sensilla or the nerves entering the central nervous system, observations in agreement with earlier studies on Calliphora. Thus, histamine seems to be a major mechanosensory transmitter candidate of the adult nervous system of Drosophila, but apparently not of Musca or Calliphora.

Animals↗
PubMed1990

A cysteine-string protein is expressed in retina and brain of Drosophila.

Antibodies can be used to identify tissue- and stage-specifically expressed genes. A monoclonal antibody MAB ab49 from a hybridoma library screened for immunohistochemical staining in the adult nervous system of Drosophila melanogaster was found to selectively bind to all neuropil regions and to synaptic boutons of motor neurons. In Western blots of homogenized brains the antibody recognizes two proteins of 32 and 34 kD. Using this antibody we have isolated seven cDNA clones that derive from two polyadenylated mRNA splice variants of a gene located at 79E1-2 on polytene chromosomes. The two mRNAs code for two inferred proteins of 249 and 223 amino acids, respectively, which are identical except for their C-terminals and a central deletion of 21 amino acids in the second protein. Both contain a contiguous string of 11 cysteine residues. In situ hybridization to frozen head sections detects expression of this gene in retina and neuronal perikarya. The 32 and 34 kD brain proteins that presumably are localized predominantly in synaptic terminals of photoreceptors and most if not all neurons may correspond to two variant cysteine-string proteins as they are of similar molecular weight and share an antigenic binding site for MAB ab49.

Amino Acid Sequence↗
PubMed1988

Cell-specific immuno-probes for the brain of normal and mutant Drosophila melanogaster. I. Wildtype visual system.

We have screened antibodies for immunocytochemical staining in the optic lobes of the brain of Drosophila melanogaster. Seven polyclonal antisera and five monoclonal antibodies are described that selectively and reproducibly stain individual cells and/or produce characteristic staining patterns in the neuropile. Such antisera are useful for the cellular characterization of molecular and structural brain defects in visual mutants. In the wildtype visual system we can at present separately stain the following: the entire complement of columnar "T1" neurons; a small set of presumptive serotonergic neurons; some 3000 cells that contain and synthesize gamma-amino butyric acid (GABA); and three groups of cells that bind antibodies to Ca2+-binding proteins. In addition, small groups of hitherto unknown tangential cells that send fine arborizations into specific strata of the medulla, and two patterns of characteristic layers in the visual neuropile have been identified by use of monoclonal antibodies generated following immunization of mice with homogenates of the brain of Drosophila melanogaster.

Animals↗
PubMed1984

Identification of [3H]deoxyglucose-labelled interneurons in the fly from serial autoradiographs.

Using the [3H]deoxyglucose technique we find in the third visual ganglion of the fly, Musca domestica, a number of neuronal profiles whose labelling strongly depends on the direction of visual movement. By reconstruction from serial autoradiographs of semithin sections the three-dimensional morphology of the labelled profiles, we demonstrate that cell bodies, neurites, axons and arborizations of two interneurons are labelled whose homologues in Calliphora have been identified as movement-sensitive centrifugal horizontal cells ('CH-cells'). A set of three other cells whose homologues in Calliphora show similar electrophysiological responses to horizontal movement ('HS-cells') exhibit very little label on either side. It is suggested that the relation between deoxyglucose mapping and physiological activity can be investigated at the cellular level by using this system of fly interneurons.

Animals↗