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Biomedical subjects

M Niethammer

Publications and source records attributed to M Niethammer.

13 recordsLinked to original sources
PubMed2003

[Quantification of cardiac function with multislice spiral CT using retrospective EKG-gating: comparison with MRI].

PURPOSE: To quantify left ventricular function derived from retrospectively ECG-gated multislice spiral CT (MSCT) data sets in comparison to MRI. MATERIALS AND METHODS: In 16 patients (14 males, 2 females, mean age 56.8 +/- 11.5 years), retrospectively ECG-gated MSCT angiography of the coronary arteries and breath-hold steady state free precession cine MRI were performed. From MSCT data-sets, 20 axial image series were reconstructed every 5 % of the RR interval. Multiplanar images were reformatted in the short axis orientation from axial images. End-systolic and end-diastolic images were selected. From these images end-systolic volume (ESV), end-diastolic volume (EDV) and stroke volume (SV) as well as the ejection fraction (EF) and myocardial mass (MM) were determined using the Simpson's method and compared with MRI. Furthermore, image quality was assessed for both imaging modalities using a four point grading scale. RESULTS: All parameters were found to have an excellent correlation between MSCT and MRI data (Pearson's correlation coefficient 0.95 - 0.99), without clinically relevant differences between both modalities. On average, the difference between both methods was 0.5 ml for ESV, 0.8 ml for EDV, 1.3 ml for SV, 0.9 % for EF and 2.3 g for MM. Image quality was slightly better for MRI (1.5 +/- 0.65) than for MSCT (1.64 +/- 0.74). CONCLUSION: Retrospectively ECG-gated MSCT angiography can not only visualize the coronary arteries but also enables precise quantification of the left ventricular function from the same MSCT data set.

Aged↗
PubMed2001

[Diagnosis of lung embolism with multislice spiral CT].

In recent years CT has been established as the method of choice for the diagnosis of central pulmonary embolism to the level of the segmental arteries. The key advantage of CT over competing modalities is the reliable detection of relevant alternative or additional disease causing the patient's symptoms. Although the clinical relevance of isolated peripheral emboli remains unclear, the alleged poor sensitivity of CT for the detection of such small clots has to date prevented the acceptance of CT as the gold standard for diagnosing pulmonary embolism. With the advent of multislice CT we can now cover the entire chest of a patient with 1-mm slices within one breath-hold. In comparison with thicker sections the detection rate of subsegmental emboli can be significantly increased with 1-mm sections. In addition the interobserver correlation which can be achieved with 1-mm sections by far exceeds the reproducibility of competing modalities. Meanwhile use of multislice CT for a combined diagnosis of pulmonary embolism and deep venous thrombosis with the same modality appears to be clinically accepted. In the vast majority of patients who receive a combined thoracic and venous multislice CT examination the scan either confirms the suspected diagnosis or reveals relevant alternative or additional disease. The therapeutic regimen is usually chosen based on the functional effect of embolic vascular occlusion. With the advent of fast CT scanning techniques, also functional parameters of lung perfusion can be non-invasively assessed by CT imaging. These advantages let multislice CT appear as an attractive modality for a non-invasive, fast, accurate and comprehensive diagnosis of pulmonary embolism, its causes, effects and differential diagnoses.

Humans↗
PubMed2001

Time-frequency representations of Lamb waves.

The objective of this study is to establish the effectiveness of four different time-frequency representations (TFRs)--the reassigned spectrogram, the reassigned scalogram, the smoothed Wigner-Ville distribution, and the Hilbert spectrum--by comparing their ability to resolve the dispersion relationships for Lamb waves generated and detected with optical techniques. This paper illustrates the utility of using TFRs to quantitatively resolve changes in the frequency content of these nonstationary signals, as a function of time. While each technique has certain strengths and weaknesses, the reassigned spectrogram appears to be the best choice to characterize multimode Lamb waves.

Journal Article↗
PubMed2001

Crack characterization using guided circumferential waves.

This paper examines the propagation of guided circumferential waves in a hollow isotropic cylinder that contains a crack, with the goal of using these guided waves to both locate and size the crack. The crack is sized using a modified Auld's formula, which relates the crack's length to a reflected energy coefficient. The crack is then located by operating on the backscattered signal with a time-frequency digital signal processing (DSP) technique, and then comparing these results to those obtained if the cylinder is perfect. The guided circumferential waves are generated with a commercial finite element method (FEM) code. One objective of this work is to demonstrate the effectiveness of using sophisticated DSP techniques to describe the effect of scattering on dispersive waves, showing it is possible to characterize cracks systematically and accurately by quantifying this scattering effect. The results show that the need for high frequency signals to detect small cracks is significantly decreased by using these techniques.

Journal Article↗
PubMed2000

NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein.

Disruption of one allele of the LIS1 gene causes a severe developmental brain abnormality, type I lissencephaly. In Aspergillus nidulans, the LIS1 homolog, NUDF, and cytoplasmic dynein are genetically linked and regulate nuclear movements during hyphal growth. Recently, we demonstrated that mammalian LIS1 regulates dynein functions. Here we characterize NUDEL, a novel LIS1-interacting protein with sequence homology to gene products also implicated in nuclear distribution in fungi. Like LIS1, NUDEL is robustly expressed in brain, enriched at centrosomes and neuronal growth cones, and interacts with cytoplasmic dynein. Furthermore, NUDEL is a substrate of Cdk5, a kinase known to be critical during neuronal migration. Inhibition of Cdk5 modifies NUDEL distribution in neurons and affects neuritic morphology. Our findings point to cross-talk between two prominent pathways that regulate neuronal migration.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2000

Regulation of cytoplasmic dynein behaviour and microtubule organization by mammalian Lis1.

Whereas total loss of Lis1 is lethal, disruption of one allele of the Lis1 gene results in brain abnormalities, indicating that developing neurons are particularly sensitive to a reduction in Lis1 dosage. Here we show that Lis1 is enriched in neurons relative to levels in other cell types, and that Lis1 interacts with the microtubule motor cytoplasmic dynein. Production of more Lis1 in non-neuronal cells increases retrograde movement of cytoplasmic dynein and leads to peripheral accumulation of microtubules. These changes may reflect neuron-like dynein behaviours induced by abundant Lis1. Lis1 deficiency produces the opposite phenotype. Our results indicate that abundance of Lis1 in neurons may stimulate specific dynein functions that function in neuronal migration and axon growth.

Animals↗
PubMed1999

[Computed tomography of the abdomen with multidetector-array CT].

BACKGROUND: The advent of multidetector CT (MDCT) constitutes a quantum leap creating a wealth of new opportunities in medical imaging. However, while the basic principles of spiral CT still apply, we are now challenged to rethink our strategies in planning a CT study to take full advantage of the increased capabilities of MDCT. MATERIALS AND METHODS: We report here our preliminary experiences with MDCT for abdominal CT imaging within a 5-month period. During this time, suitable protocols for investigation of the abdomen using MDCT were developed. The capabilities of MDCT allow for tailoring dedicated CT protocols for routine applications as well as for biphasic liver studies and CT angiography of the aorta and abdominal vessels. RESULTS: The speed of MDCT can either be used to reduce the time needed to cover a given volume, or to use narrower beam collimations to increase the resolution of detail along the z-axis and reduce volume averaging. Higher scan speed allows reduction of the amount of contrast material in vascular applications and suppression of motion artifacts. Higher spatial resolution with thinner collimations reduces volume averaging and improves the detection of small hepatic and pancreatic lesions. Detailed analysis of vascular structures and high-quality three-dimensional reformations become feasible. New problems arise from the large amount of data generated by MDCT. CONCLUSIONS: MDCT offers a wealth of new opportunities that help us to come to a fast and accurate diagnosis in suspected abdominal disease. Traditional indications for performing CT are reemphasized and new clinical applications can be exploited.

Abdomen↗
PubMed1999

Microtubule binding by CRIPT and its potential role in the synaptic clustering of PSD-95.

CRIPT is a postsynaptic protein that binds selectively to the third PDZ domain (PDZ3) of PSD-95. Here we show that CRIPT also binds directly to microtubules, thereby linking PSD-95 to the microtubule cytoskeleton. Disrupting the CRIPT-PSD-95 interaction in cultured hippocampal neurons with a PDZ3-specific peptide prevented the association of PSD-95 with microtubules and inhibited the synaptic clustering of PSD-95, chapsyn-110/PSD-93 and GKAP (a PSD-95-binding protein). However, the number of synapses and the synaptic clustering of NMDA receptors were unaffected, suggesting that PSD-95-family proteins are not essential for the maintenance of synapses and the synaptic localization of NMDA receptors.

Amino Acid Motifs↗
PubMed1998

CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90.

The synaptic protein PSD-95/SAP90 binds to and clusters a variety of membrane proteins via its two N-terminal PDZ domains. We report a novel protein, CRIPT, which is highly conserved from mammals to plants and binds selectively to the third PDZ domain (PDZ3) of PSD-95 via its C terminus. While conforming to the consensus PDZ-binding C-terminal sequence (X-S/T-X-V-COOH), residues at the -1 position and upstream of the last four amino acids of CRIPT determine its specificity for PDZ3. In heterologous cells, CRIPT causes a redistribution of PSD-95 to microtubules. In brain, CRIPT colocalizes with PSD-95 in the postsynaptic density and can be coimmunoprecipitated with PSD-95 and tubulin. These findings suggest that CRIPT may regulate PSD-95 interaction with a tubulin-based cytoskeleton in excitatory synapses.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases.

Selective concentration and anchoring of ionotropic receptors at the synapse is essential for neuronal signaling. Little is known about the molecules that mediate receptor clustering in the CNS. With use of the yeast two-hybrid system to screen a rat brain cDNA library and by in vitro binding assays, we have identified an interaction between NMDA receptor subunits 2A and 2B (NR2A and NR2B) and three distinct members of the PSD-95/SAP90 family of membrane-associated putative guanylate kinases. The interaction is mediated by binding of the C terminus of the NMDA receptor subunits to the first two PDZ (also known as GLGF or DHR) domains of PSD-95/SAP90, an abundant synaptic protein associated with the membrane cytoskeleton. PSD-95 is also known to bind and cluster Shaker-type voltage-gated K+ channels. Similarities between the C-termini of NR2 subunits and K+ channels suggest a common C-terminal binding motif for PDZ domains. These data suggest that PDZ domains can function as modules for protein-protein interactions. Members of the PSD-95 family might serve to anchor NMDA receptors to the submembrane cytoskeleton and aid in the assembly of signal transduction complexes at postsynaptic sites.

Animals↗
PubMed1995

Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases.

ANCHORING of ion channels at specific subcellular sites is critical for neuronal signalling, but the mechanisms underlying channel localization and clustering are largely unknown (reviewed in ref. 1). Voltage-gated K+ channels are concentrated in various neuronal domains, including presynaptic terminals, nodes of Ranvier and dendrites, where they regulate local membrane excitability. Here we present functional and biochemical evidence that cell-surface clustering of Shaker-subfamily K+ channels is mediated by the PSD-95 family of membrane-associated putative guanylate kinases, as a result of direct binding of the carboxy-terminal cytoplasmic tails to the K+ channel subunits to two PDZ (also known as GLGF or DHR) domains in the PSD-95 protein. The ability of PDZ domains to function as independent modules for protein-protein interaction, and their presence in other junction-associated molecules (such as ZO-1 (ref. 3) and syntrophin), suggest that PDZ-domain-containing polypeptides may be widely involved in the organization of proteins at sites of membrane specialization.

Adaptor Proteins, Signal Transducing↗